Recent advances in the treatment and monitoring of HIV-1 infection have substantially diminished HIV-associated illness and mortality; however the hepatitis C has emerged as a major co morbidity among HIV-infected patients. We are conducting studies that: (1) evaluate novel therapeutic strategies in the management of HCV-infected individuals, and (2) identify the host response characteristics that predict HCV response to existing treatment and aid in developing better future therapies. This past year, we were able to (1) determine the safety, tolerability and effectiveness of a novel regimen including twice monthly Albumin-Interferon alpha 2b along with Ribavirin to treat Hepatitis C in HIV co-infected subjects; (2) demonstrate the distinct influence of ongoing HIV replication on host immune activation profiles in Hepatitis C infected subjects; (3) demonstrate the effect of race, host genetics and baseline immune status (CD4+ T cell count) on response rates to HCV and adverse events using the pegylated Interferon-alpha and Ribavirin